Cementocyte alterations associated with experimentally induced cellular cementum apposition in <i>Hyp</i> mice

Santos, Elis Janaína Lira dos; Salmon, Cristiane R.; Chavez, Michael B.; Almeida, Amanda Bandeira de; Tan, Mingyue; Chu, Emily Y.; Sallum, Enílson Antônio; Casati, Márcio Z.; Silvério, Karina Gonzáles; Kantovitz, Kamila Rosamilia; Foster, Brian L.; Júnior, Francisco Humberto Nociti

doi:10.1002/jper.21-0119

Cited by 7 publications

(9 citation statements)

References 39 publications

(114 reference statements)

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“…During orthodontic tooth movement, the protein abundance of Cx43 in PDL cells at the compressive zone was decreased under hypoxia, and Cx43 expression showed a significant enhancement in the tension zone, suggesting that Cx43 has great importance in bone remodelling [ 18 , 19 ]. Recently, Cx43 has been identified as a protein marker of cementocytes, indicating that Cx43 may be involved in cementum formation [ 20 ]. Cx43 expression directly or indirectly activates multiple signalling pathways.…”

Section: Introductionmentioning

confidence: 99%

Connective tissue growth factor promotes cementogenesis and cementum repair via Cx43/β-catenin axis

Chen

et al. 2022

Stem Cell Res Ther

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Background Orthodontic tooth movement inevitably induces cementum resorption, which is an urgent problem for orthodontists to confront. Human periodontal ligament stem cells (hPDLSCs) exert an important role in the orthodontic tooth movement and exhibit multidirectional differentiation ability in cementum regeneration. Connective tissue growth factor (CTGF) is an important extracellular matrix protein for bone homeostasis and cell differentiation. The purpose of our study was to explore the role of CTGF in cementum repair and cementogenesis and to elucidate its underlying mechanism. Methods A cementum defect model was established by tooth movement with heavy forces, and the cementum repair effect of CTGF was observed via micro-CT, HE staining and immunohistochemical staining. RT‒qPCR, western blotting (WB), alizarin red staining and ALP activity experiments verified the mineralization ability of hPDLSCs stimulated with CTGF. The expression of Cx43 in periodontal ligament cells was detected by WB and immunofluorescence (IF) experiments after CTGF stimulation in vivo and in vitro. Subsequently, the mineralization ability of hPDLSCs was observed after application of CTGF and the small interfering RNA Si-Cx43. Additionally, co-intervention via application of the small interfering RNA Si-CTGF and the Cx43 agonist ATRA in hPDLSCs was performed to deepen the mechanistic study. Next, WB, IF experiments and co-immunoprecipitation were conducted to confirm whether CTGF triggers the Cx43/β-catenin axis to regulate cementoblast differentiation of hPDLSCs. Results Local oral administration of CTGF to the cementum defects in vivo facilitated cementum repair. CTGF facilitated the cementogenesis of hPDLSCs in a concentration-dependent manner. Cx43 acted as a downstream effector of CTGF to regulate cementoblast differentiation. Si-Cx43 reduced CTGF-induced cementoblast differentiation. The Cx43 agonist ATRA restored the low differentiation capacity induced by Si-CTGF. Further mechanistic studies showed that CTGF triggered the activation of β-catenin in a dose-dependent manner. In addition, co-localization IF analysis and co-immunoprecipitation demonstrated that Cx43 interacted with β-catenin at cell‒cell connections. Si-Cx43 attenuated the substantial expression of β-catenin induced by CTGF. The Cx43 agonist reversed the inhibition of β-catenin induced by Si-CTGF. IF demonstrated that the nuclear importation of β-catenin was related to the immense expression of Cx43 at cell‒cell junctions. Conclusions Taken together, these data demonstrate that CTGF promotes cementum repair and cementogenesis through activation of the Cx43/β-catenin signalling axis.

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Section: Introductionmentioning

confidence: 99%

Connective tissue growth factor promotes cementogenesis and cementum repair via Cx43/β-catenin axis

Chen

et al. 2022

Stem Cell Res Ther

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“…Lira Dos Santos et al ( 7 ) demonstrated that cementocytes exhibited increased nuclear size and proportion of euchromatin under orthodontic loading, and reported a significant downregulation in the expression levels of type IV collagen following orthodontic tooth movement. In addition, cementocytes are also involved in cellular cementum apposition in mice and are associated with changes in cellular ultrastructure and in the proteomic profile of the cementum ( 8 ). These findings indicate that similar to PDLc, cementocytes play important roles in the biological events of the orthodontic tooth movement and the associated EARR.…”

Section: Introductionmentioning

confidence: 99%

Dynamic alternations of RANKL/OPG ratio expressed by cementocytes in response to orthodontic‑induced external apical root resorption in a rat model

et al. 2022

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The aim of the present study was to investigate the alterations in the formation of cementocytes in response to orthodontic forces and to evaluate the contribution of these cells in the biological changes of tooth movement and associated root resorption. A total of 90 Sprague Dawley rats were randomly assigned to the control, high force, and low force groups. Intrusion forces of 10 and 50 g were applied on the rat molar to induce tooth intrusion. The tooth movement was observed from 0 to 14 days by micro-computed tomography, bone histometric analysis, tartrate-resistant acid phosphatase staining, as well as reverse transcription-quantitative PCR and immunofluorescence staining assays. The results suggested that under low force conditions, osteoclasts were distributed at a higher frequency on the bone side than on the root side. Under high force conditions, both sides suffered osteoclast infiltration. In the low force group, the cementocytes exhibited downregulated sclerostin ( SOST ) and osteoprotegerin ( OPG ) mRNA levels and a lower receptor activator of nuclear factor-κB ligand ( RANKL )/ OPG ratio over a certain period of time. The expression levels of these genes were lower compared with those of the osteocytes at each time-point. In the high force group, both cementocytes and osteocytes upregulated the SOST and RANKL/OPG ratio on days 7 and 14, while the cementocytes expressed higher levels of SOST mRNA than those noted in the osteocytes. These data suggested that cementocytes responded to the orthodontic force via modulation of the RANKL/OPG ratio and SOST expression. The biological response of cementocytes contributed to the mechanotransduction and homoeostasis of the roots under compression. Excessive forces may act as a negative factor of this regulatory role. These results expand our knowledge on the function of cementocytes.

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“…Although there are some similarities between osteocytes and cementocytes, differentiation and functions remains poorly understood [8][9][10]. The function of cementocytes in periodontal physiology was not well established.…”

Section: Introductionmentioning

confidence: 99%

“…However, it is possible that this cell type presents a regulatory role in cementum. Therefore, the cementocyte could be such a dynamic actor in cementum metabolism as the osteocyte in the bone [1,8].…”

Section: Introductionmentioning

confidence: 99%

Systemic rosiglitazone administration leads to cementocytes apoptosis in wild type mice

et al. 2021

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It has been shown that a class of drugs for diabetes control, the thiazolidinediones, leads to increased apoptosis in osteocytes. Considering the correlations between osteocytes and cementocytes, the aim of this study was to demonstrate the apoptosis on cementocytes of wild type mice that had received rosiglitazone. Twenty-four male C57BL/6 mice were divided into 3 groups: 1 control, which received only the vehicle administration via oral for 1 week (PBS+DMSO 10%) and other two groups, which received 10 mg/kg of RGZ+PBS+DMSO 10% for 1 or 2 weeks, respectively. Upon completion of the time courses, mice were killed by CO2 and the mandibles were dissected and subjected to routine histotechnical processing. The sections were analyzed through transferase-mediated dUTP nick-end labeling (TUNEL) and 4’,6- diamidino-2-phenylindole (DAPI) staining of nuclear morphology (α=0.05). Control group showed significantly lower apoptotic cells/total cells ratio when compared to the experimental groups with TUNEL and DAPI methods (p=0.010 and 0.004, respectively). TUNEL method showed approximately 20% TUNEL-positive cementocytes in control and 26% in both experimental groups, while the DAPI technique showed approximately 32% of DAPI-positive cementocytes in control and 38% to 40% in experimental groups. The rosiglitazone systemic administration can lead to cementocytes apoptosis in mice. Despite the differences between the experimental and control groups, the death of cementocytes occurred as a physiological phenomenon, important in understanding the role of these cells in periodontal tissue.

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Cementocyte alterations associated with experimentally induced cellular cementum apposition in Hyp mice

Cited by 7 publications

References 39 publications

Connective tissue growth factor promotes cementogenesis and cementum repair via Cx43/β-catenin axis

Connective tissue growth factor promotes cementogenesis and cementum repair via Cx43/β-catenin axis

Dynamic alternations of RANKL/OPG ratio expressed by cementocytes in response to orthodontic‑induced external apical root resorption in a rat model

Systemic rosiglitazone administration leads to cementocytes apoptosis in wild type mice

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